152675-28-0Relevant articles and documents
Design and synthesis of quinazolinyl acetamides for their analgesic and anti-inflammatory activities
Alagarsamy, Veerachamy,Solomon, Viswas Raja,Sulthana, Mohaideen Thasthagir,Vijay, Meduri Satyasai,Narendhar, Bandi
, p. 597 - 604 (2015)
A variety of novel 2-(substituted)-N-(4-oxo-2-phenylquinazolin-3(3H)-yl)acetamides were synthesized by the reaction of 2-chloro-N-(4-oxo-2-phenylquinazolin-3(3H)-yl)acetamide with various amines. The starting material, 2-chloro-N-(4-oxo-2-phenylquinazolin
Design, molecular docking, in vitro, and in vivo studies of new quinazolin-4(3H)-ones as VEGFR-2 inhibitors with potential activity against hepatocellular carcinoma
Eissa, Ibrahim.H.,Ibrahim, Mohammed K.,Metwaly, Ahmed M.,Belal, Amany,Mehany, Ahmed B.M.,Abdelhady, Alsayed A.,Elhendawy, Mostafa A.,Radwan, Mohamed M.,ElSohly, Mahmoud A.,Mahdy, Hazem A.
, (2020/12/21)
A series of new VEGFR-2 inhibitors were designed, synthesized and evaluated for their anti-proliferative activities against hepatocellular carcinoma (HepG-2 cell line). Compound 29b (IC50 = 4.33 ± 0.2 μg/ml) was found to be the most potent derivative as it has showed to be more active than doxorubicin (IC50 = 4.50 ± 0.2 μg/ml) and 78% of sorafenib activity (IC50 = 3.40 ± 0.25 μg/ml). The inhibitory profiles against VEGFR-2 were also assessed for the most promising candidates (16b, 20c, 22b, 24a, 24b, 28c, 28e, 29a, 29b and 29c). Compounds 29b, 29c and 29a exhibited potent inhibitory activities towards VEGFR-2 at IC50 values of 3.1 ± 0.04, 3.4 ± 0.05 and 3.7 ± 0.06 μM, respectively, comparing sorafenib (IC50 = 2.4 ± 0.05 μM). Furthermorer, compound 29b induced apoptosis and arrested the cell cycle growth at G2/M phase. Additionally, in vivo antitumor experiments revealed that compounds 29b and 29c have significant tumor growth inhibition. The test of immuno-histochemical expression of activated caspase-3 revealed that there is a time-dependent increase in cleaved caspase-3 protein expression upon exposure of HepG-2 cells to compound 29b. Moreover, the fibroblastic proliferative index test revealed that compound 29b could attenuate liver fibrosis. Docking studies also supported the results concluded from the biological screening via prediction of the possible binding interactions of the target compounds with VEGFR-2 active sites using the crystal structure of VEGFR-2 downloaded from the Protein Data Bank, (PDB ID: 2OH4) using Discovery Studio 2.5 software. Further structural optimization of the most active candidates may serve as a useful strategy for getting new lead compounds in search for powerful and selective antineoplastic agents.
Design, synthesis, molecular modeling, in vivo studies and anticancer evaluation of quinazolin-4(3H)-one derivatives as potential VEGFR-2 inhibitors and apoptosis inducers
Belal, Amany,Eissa, Ibrahim H.,El-Gamal, Kamal M. A.,El-Sharkawy, Abdou,Elhendawy, Mostafa A.,Elsohly, Mahmoud A.,Ibrahim, Mohammed K.,Mahdy, Hazem A.,Mehany, Ahmed B. M.,Metwaly, Ahmed M.,Radwan, Mohamed M.
, (2019/12/24)
Inhibiting VEGFR-2 has been set up as a therapeutic strategy for treatment of cancer. Accordingly, new quinazoline-based derivatives having the structural features of VEGFR-2 inhibitors were designed and synthesized. Anti-proliferative activities were evaluated against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) using MTT assay method. Doxorubicin and sorafenib were used as positive controls. Compounds 26b, 29a, 29b and 30 showed excellent anti-cancer activities against all cell lines. Moreover, compound 31 was the most active with IC 50 values of 3.97 ± 0.2, 4.83 ± 0.2 and 4.58 ± 0.3 μM, respectively. The most active cytotoxic agents were further evaluated in vitro for their VEGFR-2 inhibitory activities, compound 31 showed a high activity against VEGFR-2 with an IC50 value of 2.5 ± 0.04 μM, almost equal to that of sorafenib (IC50 = 2.4 ± 0.05 μM). Further studies revealed the ability of this promising quinazoline derivative 31 to induce apoptosis and arrest cell cycle growth at G2/M phase. In vivo antitumor activities of the synthesized compounds revealed that compounds 30 and 31 possessed significant tumor growth inhibition effect. Molecular docking studies were also performed and finally we can say that VEGFR-2 inhibition confers the reported cytotoxic activities.
